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SHR Neuro Cancer Cardio Lipid Metab Microb

Roth, R; Häckh, M; Schnick, T; Rommel, C; Koentges, C; Bugger, H; Domisch, C; Bristow, MR; Ambardekar, AV; McKinsey, TA; Gilsbach, R; Hein, L; Preissl, S.
Transcriptional signature of cardiac myocyte recovery in mice and human reveals persistent upregulation of epigenetic factors.
Epigenetics. 2025; 20(1):2506625 Doi: 10.1080/15592294.2025.2506625 [OPEN ACCESS]
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Co-authors Med Uni Graz
Bugger Heiko Matthias
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Abstract:
Fibrosis, cardiac remodelling, and inflammation are hallmarks of heart failure. To date, there is no available pharmacological cure for heart failure, but mechanical unloading by implantation of a left ventricular assist device (LVAD) can lead to improved cardiac function in a subset of patients. This study aimed to identify the transcriptional response of left ventricular (LV) cardiac myocytes to mechanical unloading in a mouse model of reversible LV pressure overload and in failing human hearts after LVAD implantation. We found that partial recovery of ventricular dysfunction, LV hypertrophy, and gene expression programmes occurred in mice under reversible transverse aortic constriction (rTAC). Gene expression analysis in cardiac myocytes identified a lasting repression of mitochondrial gene expression resulting in compromised fatty acid oxidation in the mouse model of reversible pressure overload and in human LV samples after LVAD therapy and a persistent upregulation of epigenetic and transcriptional regulators. These findings underpin that recovery from heart failure involves complex gene regulatory networks and that mitochondrial dysfunction remains a challenge even after mechanical unloading. Further studies are needed to investigate the functional role of these factors in reverse remodelling and recovery of failing hearts.
Find related publications in this database (using NLM MeSH Indexing)
Animals - administration & dosage
Humans - administration & dosage
Myocytes, Cardiac - metabolism
Mice - administration & dosage
Epigenesis, Genetic - administration & dosage
Heart Failure - genetics, metabolism, therapy
Male - administration & dosage
Heart-Assist Devices - administration & dosage
Up-Regulation - administration & dosage
Transcriptome - administration & dosage
Ventricular Remodeling - administration & dosage

Find related publications in this database (Keywords)
Heart failure
mechanical unloading
reverse remodeling
transcriptome
epigenetics
mitochondria
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